U.S. patent application number 16/835090 was filed with the patent office on 2021-06-24 for magnetic separator for an automated single cell sequencing system.
The applicant listed for this patent is 10x Genomics, Inc.. Invention is credited to Pratomo Alimsijah, John Richard Chevillet.
Application Number | 20210187515 16/835090 |
Document ID | / |
Family ID | 1000004884013 |
Filed Date | 2021-06-24 |
United States Patent
Application |
20210187515 |
Kind Code |
A1 |
Alimsijah; Pratomo ; et
al. |
June 24, 2021 |
MAGNETIC SEPARATOR FOR AN AUTOMATED SINGLE CELL SEQUENCING
SYSTEM
Abstract
A magnetic separator is disclosed. The magnetic separator
comprises an array of magnets configured to interact with a tube
holder plate, wherein the tube holder plate comprises an array of
tubes. The magnetic separator comprises a raised frame extending
around a periphery of the array of magnets such that the raised
frame is configured to support the tube holder plate such that the
array of tubes is suspended above the array of magnets.
Inventors: |
Alimsijah; Pratomo;
(Pleasanton, CA) ; Chevillet; John Richard;
(Pleasanton, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
10x Genomics, Inc. |
Pleasanton |
CA |
US |
|
|
Family ID: |
1000004884013 |
Appl. No.: |
16/835090 |
Filed: |
March 30, 2020 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
62953050 |
Dec 23, 2019 |
|
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|
62980768 |
Feb 24, 2020 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B03C 2201/26 20130101;
B03C 1/033 20130101; B03C 2201/18 20130101 |
International
Class: |
B03C 1/033 20060101
B03C001/033 |
Claims
1. A magnetic separator, comprising: an array of magnets configured
to interact with a tube holder plate, wherein the tube holder plate
comprises an array of tubes; and a raised frame extending around a
periphery of the array of magnets such that the raised frame is
configured to support the tube holder plate such that the array of
tubes is suspended above the array of magnets.
2. The magnetic separator of claim 1, wherein the array of tubes is
suspended above the array of magnets at a height such that each
tube does not come in contact with its corresponding magnet.
3. The magnetic separator of claim 1, wherein the array of magnets
comprises an array of ring magnets, and wherein the array of tubes
is suspended above the array of ring magnets such that the bottom
ends of the tubes are not resting within the hollow spaces of the
ring magnets at different depths.
4. The magnetic separator of claim 3, wherein the array of tubes is
suspended above the array of ring magnets such that the tube holder
plate is leveled with respect to the array of ring magnets.
5. The magnetic separator of claim 1, wherein the array of magnets
are held by a magnet holder plate, and wherein the raised frame
comprises a plurality of feet, wherein each foot fits into a
corresponding hole on the magnet holder plate such that the raised
frame is mounted on the magnet holder plate.
6. The magnetic separator of claim 5, wherein the raised frame is
mounted on the magnet holder plate such that the raised frame is
raised above the magnet holder plate.
7. The magnetic separator of claim 1, wherein the raised frame
comprises a plurality of collars, wherein each of the collars
constrains a x location and a y location of the tube holder
plate.
8. The magnetic separator of claim 7, wherein each of the collars
constrains the x location and the y location of the tube holder
plate by having a tube inserted into the collar.
9. A method, comprising: providing an array of magnets configured
to interact with a tube holder plate, wherein the tube holder plate
comprises an array of tubes; and providing a raised frame extending
around a periphery of the array of magnets such that the raised
frame is configured to support the tube holder plate such that the
array of tubes is suspended above the array of magnets.
10. The method of claim 9, wherein the array of tubes is suspended
above the array of magnets at a height such that each tube does not
come in contact with its corresponding magnet.
11. The method of claim 9, wherein the array of magnets comprises
an array of ring magnets, and wherein the array of tubes is
suspended above the array of ring magnets such that the bottom ends
of the tubes are not resting within the hollow spaces of the ring
magnets at different depths.
12. The method of claim 11, wherein the array of tubes is suspended
above the array of ring magnets such that the tube holder plate is
leveled with respect to the array of ring magnets.
13. The method of claim 9, wherein the array of magnets are held by
a magnet holder plate, and wherein the raised frame comprises a
plurality of feet, wherein each foot fits into a corresponding hole
on the magnet holder plate such that the raised frame is mounted on
the magnet holder plate.
14. The method of claim 13, wherein the raised frame is mounted on
the magnet holder plate such that the raised frame is raised above
the magnet holder plate.
15. The method of claim 9, wherein the raised frame comprises a
plurality of collars, wherein each of the collars constrains a x
location and a y location of the tube holder plate.
16. The method of claim 15, wherein each of the collars constrains
the x location and the y location of the tube holder plate by
having a tube inserted into the collar.
Description
CROSS REFERENCE TO OTHER APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent
Application No. 62/953,050 entitled AUTOMATED SINGLE CELL
SEQUENCING SYSTEM filed Dec. 23, 2019 and U.S. Provisional Patent
Application No. 62/980,768 entitled MAGNETIC SEPARATOR FOR AN
AUTOMATED SINGLE CELL SEQUENCING SYSTEM filed Feb. 24, 2020, both
of which are incorporated herein by reference for all purposes.
BACKGROUND OF THE INVENTION
[0002] Ribonucleic acid (RNA) is a polymeric molecule essential in
various biological roles in coding, decoding, regulation and
expression of genes. RNA-sequencing (RNA-Seq) uses next-generation
sequencing (NGS) to reveal the presence and quantity of RNA in a
biological sample at a given moment. RNA-Seq analyzes the
transcriptome of gene expression patterns encoded within the
RNA.
[0003] Traditional RNA-Seq techniques analyze the RNA of an entire
population of cells, but only yield a bulk average of the
measurement instead of representing each individual cell's
transcriptome. By analyzing the transcriptome of a single cell at a
time, the heterogeneity of a sample is captured and resolved to the
fundamental unit of living organisms--the cell. Single-cell
transcriptomics examines the gene expression level of individual
cells in a given population by simultaneously measuring the
messenger RNA (mRNA) concentration of hundreds to thousands of
genes.
[0004] Automated single cell sequencing systems have been developed
integrating various components to achieve RNA sequencing. One
important component is a magnetic separator which interacts with a
fluid in a vial. There is a need to improve the interaction in a
way that allows fluid to be used efficiently and to provide
consistent results.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] Various embodiments of the invention are disclosed in the
following detailed description and the accompanying drawings.
[0006] FIG. 1 illustrates a front view of one embodiment of an
automated single cell sequencing system 100.
[0007] FIG. 2 illustrates another view of one embodiment of an
automated single cell sequencing system 200.
[0008] FIG. 3 illustrates yet another view of one embodiment of an
automated single cell sequencing system 300.
[0009] FIG. 4A illustrates a top view of an embodiment of a
magnetic separator plate 402.
[0010] FIG. 4B illustrates a cross sectional view of the magnetic
separator plate 402.
[0011] FIG. 4C illustrates another view of the magnetic separator
plate 402.
[0012] FIG. 5 illustrates a plurality of strip tubes 502 that may
be loaded onto the magnetic separator plate 214 where the magnetic
bead based cleanup may be performed.
[0013] FIG. 6 illustrates an exemplary consumable 602 that may be
loaded onto the magnetic separator plate 214 where the magnetic
bead based cleanup may be performed.
[0014] FIG. 7A illustrates a top view of the 96-tube PCR plate 602
being loaded onto the magnetic separator plate 402.
[0015] FIG. 7B illustrates a cross sectional view of the 96-tube
PCR plate 602 being loaded onto the magnetic separator plate
402.
[0016] FIG. 7C illustrates a portion of a magnified cross sectional
view of the 96-tube PCR plate 602 being loaded onto the magnetic
separator plate 402.
[0017] FIG. 8A illustrates a top view of a magnetic separator plate
adapter 802.
[0018] FIG. 8B illustrates a cross sectional view of the magnetic
separator plate adapter 802.
[0019] FIG. 8C illustrates a bottom view of the magnetic separator
plate adapter 802.
[0020] FIG. 8D illustrates another view of the top surface of the
magnetic separator plate adapter 802.
[0021] FIG. 8E illustrates another view of the bottom surface of
the magnetic separator plate adapter 802.
[0022] FIG. 9A illustrates a top view of the magnetic separator
plate adapter 802 being loaded onto the magnetic separator plate
402.
[0023] FIG. 9B illustrates a cross sectional view of the magnetic
separator plate adapter 802 being loaded onto the magnetic
separator plate 402.
[0024] FIG. 9C illustrates another cross sectional view of the
magnetic separator plate adapter 802 being loaded onto the magnetic
separator plate 402.
[0025] FIG. 9D illustrates a portion of a magnified cross sectional
view of the magnetic separator plate adapter 802 being loaded onto
the magnetic separator plate 402.
[0026] FIG. 10A illustrates a view of the magnetic separator plate
adapter 802 about to be loaded onto the magnetic separator plate
402 and the 96-tube PCR plate 602 about to be loaded onto the
magnetic separator plate adapter 802.
[0027] FIG. 10B illustrates another view of the magnetic separator
plate adapter 802 being loaded onto the magnetic separator plate
402 and the 96-tube PCR plate 602 being loaded onto the magnetic
separator plate adapter 802.
[0028] FIG. 11A illustrates a top view of the magnetic separator
plate adapter 802 being loaded onto the magnetic separator plate
402, and the 96-tube PCR plate 602 being loaded onto the magnetic
separator plate adapter 802.
[0029] FIG. 11B illustrates a cross sectional view of the magnetic
separator plate adapter 802 being loaded onto the magnetic
separator plate 402, and the 96-tube PCR plate 602 being loaded
onto the magnetic separator plate adapter 802.
[0030] FIG. 11C illustrates another cross-sectional view of the
magnetic separator plate adapter 802 being loaded onto the magnetic
separator plate 402, and the 96-tube PCR plate 602 being loaded
onto the magnetic separator plate adapter 802.
[0031] FIG. 11D illustrates a portion of a magnified cross
sectional view of the magnetic separator plate adapter 802 being
loaded onto the magnetic separator plate 402, and the 96-tube PCR
plate 602 being loaded onto the magnetic separator plate adapter
802.
DETAILED DESCRIPTION
[0032] The invention can be implemented in numerous ways, including
as a process; an apparatus; a system; a composition of matter; a
computer program product embodied on a computer readable storage
medium; and/or a processor, such as a processor configured to
execute instructions stored on and/or provided by a memory coupled
to the processor. In this specification, these implementations, or
any other form that the invention may take, may be referred to as
techniques. In general, the order of the steps of disclosed
processes may be altered within the scope of the invention. Unless
stated otherwise, a component such as a processor or a memory
described as being configured to perform a task may be implemented
as a general component that is temporarily configured to perform
the task at a given time or a specific component that is
manufactured to perform the task. As used herein, the term
`processor` refers to one or more devices, circuits, and/or
processing cores configured to process data, such as computer
program instructions.
[0033] A detailed description of one or more embodiments of the
invention is provided below along with accompanying figures that
illustrate the principles of the invention. The invention is
described in connection with such embodiments, but the invention is
not limited to any embodiment. The scope of the invention is
limited only by the claims and the invention encompasses numerous
alternatives, modifications and equivalents. Numerous specific
details are set forth in the following description in order to
provide a thorough understanding of the invention. These details
are provided for the purpose of example and the invention may be
practiced according to the claims without some or all of these
specific details. For the purpose of clarity, technical material
that is known in the technical fields related to the invention has
not been described in detail so that the invention is not
unnecessarily obscured.
[0034] Preparing consistent single cell gene expression libraries
is labor intensive and requires extensive hands-on (i.e., manual)
time. It would be beneficial if this could be automated, freeing
lab personnel to perform other tasks.
[0035] Automated techniques for the preparation of single cell gene
expression libraries are disclosed in the present application. The
techniques provided herein allow for the maximization of
consistency in the libraries prepared and productivity of the
personnel. The techniques improve quality and performance by 1)
decreasing technical variability and generating reproducible
results; 2) running pre-validated protocols for single cell assays;
and 3) providing a robust workflow and ready-to-use solution. The
techniques save time and resources by 1) reducing hands-on time in
the lab; 2) eliminating the need for dedicated resources; and 3)
requiring no specialized expertise. The techniques are integrated
and validated. Single cell partitioning, barcoding, and library
preparation are integrated together in one optimized instrument. As
a result, less customization and optimization are needed, thereby
improving productivity.
[0036] FIG. 1 illustrates a front view of one embodiment of an
automated single cell sequencing system 100. The system includes an
automated controller 102 on deck for single cell partitioning and
barcoding. Reagents and consumables may be loaded onto the deck
area 104 at the beginning of each run. Operations may be guided
through an easy-to-use touchscreen computer 106 with Internet
connectivity. System 100 includes a liquid handling gantry 108 that
may perform pipetting steps throughout the entire single cell
workflow. System 100 further includes one or more barcode scanners
that enable lot and reagent tracking for reagents and
consumables.
[0037] FIG. 2 illustrates another view of one embodiment of an
automated single cell sequencing system 200. Automated single cell
sequencing system 200 includes five carriers (202, 204, 206, 208,
and 210) on the deck 201. Some of the carriers are stationary and
some of the carriers may slide in and out for loading and unloading
items. Each of the carriers may be loaded with different types of
labwares, modules, and consumables, such as a magnetic separator
plate, a thermal cycler block, tips, reagent reservoirs, plates
(e.g., polymerase chain reaction (PCR) plates and deep well
plates), tubes, and the like. The terms labwares and modules may be
used interchangeably in the present application.
[0038] FIG. 3 illustrates yet another view of one embodiment of an
automated single cell sequencing system 300. Automated single cell
sequencing system 300 includes five carriers (302, 304, 306, 308,
and 310) and a disposal bin 336 on a deck 301.
[0039] As shown in FIG. 2, an automated controller 212 for single
cell partitioning and barcoding is located adjacent to the left
most carrier 202. The leftmost carrier 202 includes a magnetic
separator plate 214. An array of magnets 218 is located above
magnetic separator plate 214. Arrays of wells, tips or tubes may be
placed above the array of magnets 218. In some embodiments, a
magnetic separator plate adapter 217 may be mounted on top of the
magnetic separator plate 214 to keep the array of tips/tubes stable
and sitting at the exact locations. The magnetic separator plate
adapter 217 may rest above the magnetic separator plate 214 and the
array of magnets 218. The magnetic separator plate adapter 217 may
be formed of plastic and include skirts. Magnetic separator plate
adapter 217 may include a plurality of calibration posts 216.
Carrier 202 may further receive a cold plate reagent module 220 and
other reagent modules 222.
[0040] In some embodiments, automated single cell sequencing system
200 may include a barcode reading system. A barcode reader is used
to scan reagents and consumables. The barcode reading system
enables experiment tracking and prevents reagent mix-ups. A barcode
reader (not shown in FIG. 2) may be placed above the five carriers
(202, 204, 206, 208, and 210) on deck 201. The barcode reader may
be used to read the slots for holding the tips/tubes and the
tips/tubes that go into the slots at different locations. The
barcode reading system may include software logic to make sure that
the right tubes (with reagents) are put at the right slots. The
barcode reading system may also detect that the tubes are missing
such that the system may inform the user about these errors. The
system may check for color matching, lot numbers, and expiration
dates. As shown in FIG. 2, automated single cell sequencing system
200 may include a plurality of mirrors 223 to allow the barcode
reader to read sideways and at more locations. In some embodiments,
stickers with barcodes on the slots are covered by the tips/tubes
if they are placed there. If the barcode reader reads the barcodes
on the slots, then the slots are determined as being empty. If the
barcode reader reads the barcodes on the tips/tubes, then the
system may match the two barcodes.
[0041] Carrier 204 (the second carrier from the left) includes an
on-deck thermal cycler 224 (ODTC). A thermal cycler may be used to
amplify segments of Deoxyribonucleic acid (DNA) via the polymerase
chain reaction (PCR). Thermal cyclers may also be used to
facilitate other temperature-sensitive reactions. In some
embodiments, a thermal cycler has a thermal block with holes where
tubes holding reaction mixtures may be inserted. The thermal cycler
then raises and lowers the temperature of the block in discrete,
pre-programmed steps. Carrier 204 further includes a rack 226 for
storing disposable ODTC lids.
[0042] Carrier 206 (the third carrier from the left) includes
carrier spaces for receiving, storing, or loading tube strips,
chips, gel beads, core or lifting paddles, ethanol reservoirs,
primer, glycerol, and the like. Carrier 208 (the fourth carrier
from the left) includes a sample index plate holder 230. The
carrier further includes a unit 232 for formulations and bead
cleanups. Carrier 208 and carrier 210 (the fifth carrier from the
left) may receive different consumables, such as pipette tips
234.
[0043] Automated single cell sequencing system 200 may further
include a waste disposal bin 236 that is adjacent to carrier 210.
In some embodiments, a divider may be added to the waste disposal
bin for separating the recycled tips and lids. With the added
divider, one side of the disposal bin is used for storing the tips
and the other side of the disposal bin is used for storing the
lids. A gantry 238 may be programmed to drop the tips and the lids
on different sides of the disposal bin. This prevents the lids from
stacking up and toppling over, causing the system to malfunction.
This allows the recycling of the lids while preventing
contamination.
[0044] The liquid handling gantry 238 in automated single cell
sequencing system 200 may perform automated pipetting steps
throughout the entire single cell workflow. Liquid handling gantry
238 is a movable liquid-handling pipetting device with precision
positioning.
[0045] A traditional manual pipette is a laboratory tool commonly
used in chemistry, biology and medicine to transport a measured
volume of liquid. A pipette can be used to aspire (or draw up) a
liquid into a pipette tip and dispense the liquid. In manual
pipetting, a piston is moved by a thumb using an operation knob.
Accuracy and precision of pipetting depend on the expertise of the
human operator.
[0046] Automated pipetting has many advantages over manual
pipetting. Automated pipetting enhances the throughput and the
reproducibility of laboratory experiments. Automated pipetting
takes the manual labor out of repeated pipetting, thereby
shortening manual hands-on time. Reducing manual hands-on time
frees up time and effort for other tasks, thereby greatly improving
throughput. Furthermore, automated pipetting significantly reduces
errors from manual pipetting, thereby enhancing
reproducibility.
[0047] The liquid handling gantry 238 in automated single cell
sequencing system 200 includes a pipetting head, which is the
mechanical component for liquid transfer. In some embodiments, the
pipetting head is a multi-channel pipetting head for increased
throughput. In some embodiments, the pipetting head may be an
8-channel pipetting head coupled to a pump system such that for
each channel, a volume of liquid may be aspirated from a source
container by creating suction and then dispensed into a destination
container (e.g., a tube or a well). A disposable tip may be
attached to each of the eight channels of the pipetting head, such
that the liquid is not in direct contact with the pipetting head,
preventing cross contamination.
[0048] The liquid handling gantry 238 with the pipetting head may
be programmed to move within a working area where liquid aspirating
and dispensing take place. The working area may be the deck area
201 including the five carriers (202, 204, 206, 208, and 210) that
may be loaded with different types of labwares, modules, or
consumables, such as reagent reservoirs, plates (e.g., polymerase
chain reaction (PCR) plates and deep well plates), tubes, and the
like. For example, the pipetting head may be moved to the position
of the reagent module 240 to dispense liquid into a row 242 of
eight wells of the reagent module 240. The position of the reagent
module 240 and the position of the row of wells may each be
specified by a set of offset distances in the x, y, and z axes from
one or more reference points within deck area 201. In some
embodiments, the position of a certain module or labware may be
recorded by single cell sequencing system 200 as a first set of
offset values (in x, y, and z) from a reference point within deck
area 201, and the position of a row of wells within the module or
labware may further be recorded by the system as another set of
offset values from the position of the module or labware. In some
embodiments, different positions within the working area are
recorded by single cell sequencing system 200 as different sets of
offset values from a single reference point within deck area
201.
[0049] In order to place the pipetting head into the appropriate
source and destination containers, the liquid handling gantry 238
with the pipetting head may be moved by one or more actuators to
different x and y positions in a plane substantially parallel to
the floor of deck 201. In addition, the pipetting head may be moved
by one or more actuators in a direction substantially perpendicular
to the plane, such that the pipetting head and the tips attached to
the pipetting head may be inserted into or withdrawn from the
source and destination containers.
[0050] Magnetic separator plate 214 in FIG. 2 performs magnetic
bead based cleanup. Magnetic beads are used for DNA purification
and fragment size selection. Automated single cell sequencing
system 200 uses the single-cell RNA-seq technology to analyze
transcriptomes on a cell-by-cell basis through the use of
microfluidic partitioning to capture single cells and prepare
barcoded, next-generation sequencing (NGS) cDNA libraries.
Specifically, single cells, reverse transcription (RT) reagents,
gel beads containing barcoded oligonucleotides, and oil are
combined on a microfluidic chip to form reaction vesicles called
Gel Beads in Emulsion, or GEMs. After incubation, GEMs are broken
and pooled fractions are recovered. Silane magnetic beads are used
to purify the first-strand cDNA from the post GEM-RT reaction
mixture, which includes leftover biochemical reagents and primers.
In particular, consumables (e.g., test tubes or wells) containing
the post GEM-RT reaction mixture and the magnetic beads may be
loaded onto the magnetic separator plate 214 where the magnetic
bead based cleanup is performed. Barcoded, full-length cDNA is then
amplified via PCR to generate sufficient mass for library
construction.
[0051] FIG. 4A illustrates a top view of an embodiment of a
magnetic separator plate 402. FIG. 4B illustrates a cross sectional
view of the magnetic separator plate 402. FIG. 4C illustrates
another view of the magnetic separator plate 402.
[0052] As shown in FIG. 4A, magnetic separator plate 402 is a
magnet holder plate that holds an array of magnets 404. Magnetic
separator plate 402 is a 96-ring magnet plate, and the array of
magnets 404 is an 8.times.12 array of magnets with eight magnets in
a row and twelve magnets in a column. In some embodiments, each of
the magnets 404 is a ring magnet. As shown in FIG. 4B, a ring
magnet may be a magnet with a shape of a hollow cylinder that is
empty from inside and with differing internal and external radii.
The hollow space of the cylinder allows a bottom end of a tube to
be inserted therein. For example, a tube received by a ring magnet
may be a finger-like length of glass or plastic tubing that is open
at the top and closed at the bottom.
[0053] FIG. 5 illustrates a plurality of strip tubes 502 that may
be loaded onto the magnetic separator plate 214 or magnetic
separator plate 402 where the magnetic bead based cleanup may be
performed. As shown in FIG. 5, each of the strip tubes 502 includes
eight tubes 504 for storing the reaction mixture and the magnetic
beads.
[0054] FIG. 6 illustrates an exemplary consumable 602 that may be
loaded onto the magnetic separator plate 214 or magnetic separator
plate 402 where the magnetic bead based cleanup may be performed.
In this example, consumable 602 is a 96-tube polymerase chain
reaction (PCR) tube holder plate with an array of tubes 604
arranged as an 8.times.12 array of tubes with eight tubes in a row
and twelve tubes in a column.
[0055] FIG. 7A illustrates a top view of the 96-tube PCR plate 602
being loaded onto the magnetic separator plate 402. FIG. 7B
illustrates a cross sectional view of the 96-tube PCR plate 602
being loaded onto the magnetic separator plate 402. FIG. 4C
illustrates a portion of a magnified cross-sectional view of the
96-tube PCR plate 602 being loaded onto the magnetic separator
plate 402.
[0056] As shown in FIGS. 7B and 7C, the hollow space of a ring
magnet (e.g., 404A or 404B) allows the bottom end of a tube (e.g.,
604A or 604B) to be inserted therein. However, both the PCR plate
602 and the magnetic separator plate 402 are manufactured parts
that have their respective sets of associated tolerances. All
dimensions of a manufactured part have their associated tolerance,
the amount that the particular dimension is allowed to vary. The
tolerance is the difference between the maximum and minimum limits.
Therefore, the length 606A (the length from the center of the ring
magnet 404A to the center of the ring magnet 404B) and the length
606B (the length from the center of the ring magnet 404B to the
center of the ring magnet 404C) may not be the same. Similarly, the
length 608A (the length from the center of the tube 604A to the
center of the tube 604B) and the length 608B (the length from the
center of the tube 608B to the center of the tube 604C) may not be
the same. These variations in dimensions may cause misalignments of
the tubes and their corresponding ring magnets. As a result, some
of the bottom ends of the tubes may no longer be inserted into the
hollow spaces and resting within the hollow spaces of the ring
magnets at the same depth, causing the PCR plate 602 to be tilted
instead of leveled, and causing it to rest on the magnetic
separator plate 402 at an angle, thereby degrading the performance
of the magnetic bead based cleanup process.
[0057] In the present application, an improved magnetic separator
is disclosed. The magnetic separator comprises an array of magnets
configured to interact with an array of tubes, wherein the array of
tubes is attached to a plate. The magnetic separator further
includes a magnetic separator plate adapter. In some embodiments,
the adapter comprises a raised frame extending around a periphery
of the array of magnets such that the raised frame is configured to
support the plate, such that the array of tubes are suspended above
the array of magnets. By suspending the array of tubes above the
array of magnets, the bottom ends of the tubes are no longer
resting within the hollow spaces of the ring magnets at different
depths, thereby keeping the plate with the array of tubes leveled
with respect to the array of magnets. The benefit is that the
performance of the magnetic bead based cleanup process may be
significantly improved.
[0058] FIG. 8A illustrates a top view of a magnetic separator plate
adapter 802. FIG. 8B illustrates a cross sectional view of the
magnetic separator plate adapter 802. FIG. 8C illustrates a bottom
view of the magnetic separator plate adapter 802. FIG. 8D
illustrates another view of the top surface of the magnetic
separator plate adapter 802. FIG. 8E illustrates another view of
the bottom surface of the magnetic separator plate adapter 802. As
shown in FIG. 8A, magnetic separator plate adapter 802 includes
four collars 804 at the four corners of the adapter. The collars
804 may be used to fix the location (the x and y location on the
deck) of a consumable, such as a 96-tube PCR plate. For example,
each of the collars 804 constrains the x location and the y
location of the tube holder plate by having a tube inserted into
the collar. The magnetic separator plate adapter 802 further
includes four cylindrical feet 806 at the four corners of the
adapter, such that the magnetic separator plate adapter 802 may be
mounted on the magnetic separator plate 402. In some embodiments,
magnetic separator plate adapter 802 may be formed of plastic and
includes skirts. Magnetic separator plate adapter 802 may include a
plurality of calibration posts 808.
[0059] FIG. 9A illustrates a top view of the magnetic separator
plate adapter 802 being loaded onto the magnetic separator plate
402. FIG. 9B illustrates a cross sectional view of the magnetic
separator plate adapter 802 being loaded onto the magnetic
separator plate 402. FIG. 9C illustrates another cross sectional
view of the magnetic separator plate adapter 802 being loaded onto
the magnetic separator plate 402. FIG. 9D illustrates a portion of
a magnified cross sectional view of the magnetic separator plate
adapter 802 being loaded onto the magnetic separator plate 402. As
shown in FIGS. 9B, 9C, and 9D, a cylindrical foot 806 of the
magnetic separator plate adapter 802 fits into a cylindrical hole
on the magnetic separator plate 402, thereby mounting the magnetic
separator plate adapter 802 on the magnetic separator plate 402 and
raising the magnetic separator plate adapter 802 above the magnetic
separator plate 402.
[0060] FIG. 10A illustrates a view of the magnetic separator plate
adapter 802 about to be loaded onto the magnetic separator plate
402 and the 96-tube PCR plate 602 about to be loaded onto the
magnetic separator plate adapter 802. FIG. 10B illustrates another
view of the magnetic separator plate adapter 802 being loaded onto
the magnetic separator plate 402 and the 96-tube PCR plate 602
being loaded onto the magnetic separator plate adapter 802.
[0061] FIG. 11A illustrates a top view of the magnetic separator
plate adapter 802 being loaded onto the magnetic separator plate
402, and the 96-tube PCR plate 602 being loaded onto the magnetic
separator plate adapter 802. FIG. 11B illustrates a cross-sectional
view of the magnetic separator plate adapter 802 being loaded onto
the magnetic separator plate 402, and the 96-tube PCR plate 602
being loaded onto the magnetic separator plate adapter 802. FIG.
11C illustrates another cross-sectional view of the magnetic
separator plate adapter 802 being loaded onto the magnetic
separator plate 402, and the 96-tube PCR plate 602 being loaded
onto the magnetic separator plate adapter 802. FIG. 11D illustrates
a portion of a magnified cross-sectional view of the magnetic
separator plate adapter 802 being loaded onto the magnetic
separator plate 402, and the 96-tube PCR plate 602 being loaded
onto the magnetic separator plate adapter 802
[0062] The magnetic separator plate adapter 802 comprises a raised
frame extending around the periphery of the magnetic separator
plate 402, such that the raised frame supports the 96-tube PCR
plate 602 in such a way that the array of tubes 604 are suspended
above the array of magnets 404. As shown in FIG. 11D, the array of
tubes is suspended above the array of magnets 404 at a height such
that the tubes 604 do not come in contact with their corresponding
magnets 404. By suspending the array of tubes 604 above the array
of magnets 404, the bottom ends of the tubes 604 are no longer
resting within the hollow spaces of the ring magnets at different
depths, thereby keeping the 96-tube PCR plate 602 with the array of
tubes 604 leveled with respect to the array of magnets 404. The
benefit is that the performance of the magnetic bead based cleanup
process may be significantly improved.
[0063] Although the foregoing embodiments have been described in
some detail for purposes of clarity of understanding, the invention
is not limited to the details provided. There are many alternative
ways of implementing the invention. The disclosed embodiments are
illustrative and not restrictive.
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